Nilsson Fredrik Y, Tolmachev Vladimir
Affibody AB, Box 20137, Voltav 13, SE-161 02 Bromma, Sweden.
Curr Opin Drug Discov Devel. 2007 Mar;10(2):167-75.
Molecular imaging shows promise as a useful tool to aid drug discovery and development and also to provide important prognostic and predictive diagnostic information affecting patient management in the clinic. However, the use of molecular imaging diagnostically is not widely adopted, in part due to the lack of suitable targeting agents. Affibody molecules are a class of small and very stable protein domains, which can be used to selectively address a wide range of protein targets. Their small size enables high contrast radionuclide imaging and they can be produced by conventional peptide synthesis methods. Their potential utility in molecular imaging is highlighted in a large number of animal studies using anti-HER2 Affibody tracers and has recently been validated in breast cancer patients with HER2-expressing metastases. The therapeutic efficacy of the Affibody molecules in this indication was demonstrated in preclinical models using a targeted radionuclide as the effector function. This review will focus on the recent use of Affibody molecules for molecular imaging and their application for radioimmunotherapy.
分子成像有望成为辅助药物研发的有用工具,还能提供重要的预后和预测诊断信息,从而影响临床患者管理。然而,分子成像在诊断方面的应用尚未广泛采用,部分原因是缺乏合适的靶向剂。亲和体分子是一类小而非常稳定的蛋白质结构域,可用于选择性地靶向多种蛋白质靶点。它们的小尺寸使其适用于高对比度放射性核素成像,并且可以通过传统的肽合成方法生产。在大量使用抗HER2亲和体示踪剂的动物研究中突出了它们在分子成像中的潜在效用,并且最近在患有HER2表达转移的乳腺癌患者中得到了验证。在临床前模型中使用靶向放射性核素作为效应功能证明了亲和体分子在该适应症中的治疗效果。本综述将重点关注亲和体分子在分子成像中的最新应用及其在放射免疫治疗中的应用。